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Science (New York, N.Y.) Oct 2014Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the...
Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.
Topics: Aging; Animals; Brain; Choroid Plexus; Cognition; Gene Expression Regulation; Hippocampus; Interferon Regulatory Factors; Interferon Type I; Mice; Mice, Transgenic; Neurogenesis; Receptors, Interferon; Interferon gamma Receptor
PubMed: 25147279
DOI: 10.1126/science.1252945 -
Acta Neuropathologica Communications Sep 2014This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily... (Review)
Review
This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer's disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial pathology and its significance during aging and in the pathogenesis of Alzheimer dementia (AD). The identification of dystrophic (senescent) microglia has created an ostensible conflict with prior work claiming a role for activated microglia and neuroinflammation during normal aging and in AD, and this has raised a basic question: does the brain's immune system become hyperactive (inflamed) or does it become weakened (senescent) in elderly and demented people, and what is the impact on neuronal function and cognition? Here we strive to reconcile these seemingly contradictory notions by arguing that both low-grade neuroinflammation and microglial senescence are the result of aging-associated free radical injury. Both processes are damaging for microglia as they synergistically exhaust this essential cell population to the point where the brain's immune system is effete and unable to support neuronal function.
Topics: Alzheimer Disease; Brain; Humans; Microglia
PubMed: 25257319
DOI: 10.1186/s40478-014-0142-6 -
Neuromolecular Medicine Sep 2022Our perception of distinct structures in brain cells and understanding of their function has been revised and updated overtime. Past approaches combined with current... (Review)
Review
Our perception of distinct structures in brain cells and understanding of their function has been revised and updated overtime. Past approaches combined with current powerful technologies provide a more complete picture of the brain's organization, from how the neurons connect with each other to finer details of every corner inside the neurons.
Topics: Brain; Neurons
PubMed: 35083700
DOI: 10.1007/s12017-021-08701-y -
Neuron Jan 2014Neural ensembles oscillate across a broad range of frequencies and are transiently coupled or "bound" together when people attend to a stimulus, perceive, think, and... (Review)
Review
Neural ensembles oscillate across a broad range of frequencies and are transiently coupled or "bound" together when people attend to a stimulus, perceive, think, and act. This is a dynamic, self-assembling process, with parts of the brain engaging and disengaging in time. But how is it done? The theory of Coordination Dynamics proposes a mechanism called metastability, a subtle blend of integration and segregation. Tendencies for brain regions to express their individual autonomy and specialized functions (segregation, modularity) coexist with tendencies to couple and coordinate globally for multiple functions (integration). Although metastability has garnered increasing attention, it has yet to be demonstrated and treated within a fully spatiotemporal perspective. Here, we illustrate metastability in continuous neural and behavioral recordings, and we discuss theory and experiments at multiple scales, suggesting that metastable dynamics underlie the real-time coordination necessary for the brain's dynamic cognitive, behavioral, and social functions.
Topics: Animals; Brain; Humans; Models, Neurological; Neural Pathways; Neuronal Plasticity; Neurons
PubMed: 24411730
DOI: 10.1016/j.neuron.2013.12.022 -
Acta Neuropathologica Communications Jun 2021Alzheimer's disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have...
Alzheimer's disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients.
Topics: Alzheimer Disease; Animals; Brain; Disease Models, Animal; Female; Glymphatic System; Male; Maze Learning; Mice; Mice, Transgenic; Transcranial Magnetic Stimulation
PubMed: 34078467
DOI: 10.1186/s40478-021-01198-3 -
Proceedings of the National Academy of... Jan 2014Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition... (Comparative Study)
Comparative Study
Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8-22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.
Topics: Adolescent; Brain; Child; Connectome; Diffusion Tensor Imaging; Female; Humans; Linear Models; Male; Sex Characteristics; Young Adult
PubMed: 24297904
DOI: 10.1073/pnas.1316909110 -
Gerontology 2018In this mini-review, we survey the extant literature on brain aging, with the emphasis on longitudinal studies of neuroanatomy, including regional brain volumes and... (Review)
Review
In this mini-review, we survey the extant literature on brain aging, with the emphasis on longitudinal studies of neuroanatomy, including regional brain volumes and white matter microstructure. We assess the impact of vascular, metabolic, and inflammatory risk factors on the trajectories of change in regional brain volumes and white matter properties, as well as the relationships between neuroanatomical and physiological changes and their influence on cognitive performance. We examine these findings in the context of current biological theories of aging and propose the means of integrating noninvasive measures - spectroscopic indices of brain energy metabolism and regional iron deposits - as valuable proxies for elucidating the basic neurobiology of human brain aging. In a brief summary of the recent findings pertaining to age-related changes in the brain structure and their impact on cognition, we discuss the role of vascular, metabolic, and inflammatory risk factors in shaping the trajectories of change. Drawing on the extant biological theories of aging and mindful of the brain's role as a disproportionately voracious energy consumer in mammals, we emphasize the importance of the fundamental bioenergetic mechanisms as drivers of age-related changes in brain structure and function. We sketch out a model that builds on the conceptualization of aging as an expression of cumulative cellular damage inflicted by reactive oxygen species and ensuing declines in energy metabolism. We outline the ways and means of adapting this model, Free-Radical-Induced Energetic and Neural Decline in Senescence (FRIENDS), to human aging and testing it within the constraints of noninvasive neuroimaging.
Topics: Aging; Animals; Brain; Cognition; Diffusion Tensor Imaging; Energy Metabolism; Free Radicals; Functional Neuroimaging; Homeostasis; Humans; Iron; Longitudinal Studies; Magnetic Resonance Imaging; Models, Neurological; White Matter
PubMed: 28858861
DOI: 10.1159/000479508 -
Current Biology : CB Oct 2023Giant brains have independently evolved twice on this planet, in vertebrates and in cephalopods (Figure 1A). Thus, the brains and nervous systems of cephalopods provide... (Review)
Review
Giant brains have independently evolved twice on this planet, in vertebrates and in cephalopods (Figure 1A). Thus, the brains and nervous systems of cephalopods provide an important counterpoint to vertebrates in the search for generalities of brain organization and function. Their mere existence disproves various hypotheses proposed to explain the evolution of the mind and the human brain, such as cognition and large brains evolved only in long-lived animals with complex social systems and parental care, none of which is true of cephalopods. Therefore, it is worthwhile to review what is known about the evolution of cephalopod nervous systems to consider how it informs our understanding of general principles of brain evolution.
Topics: Animals; Humans; Brain; Cephalopoda
PubMed: 37875089
DOI: 10.1016/j.cub.2023.08.092 -
Neuron Sep 2014The human connectome will provide a detailed mapping of the brain's connectivity, with fundamental insights for health and disease. However, further understanding of... (Review)
Review
The human connectome will provide a detailed mapping of the brain's connectivity, with fundamental insights for health and disease. However, further understanding of brain function and dysfunction will require an integrated framework that links brain connectivity with brain dynamics, as well as the biological details that relate this connectivity more directly to function. In this Perspective, we describe such a framework for studying the brain's "dynome" and its relationship to cognition.
Topics: Brain; Connectome; Humans; Models, Neurological
PubMed: 25233314
DOI: 10.1016/j.neuron.2014.08.016 -
Oxidative Medicine and Cellular... 2018
Topics: Animals; Brain; Cell Proliferation; Cells, Cultured; Humans; Models, Biological; Neurodegenerative Diseases; Oxidation-Reduction; Plant Extracts; Polyphenols
PubMed: 30159116
DOI: 10.1155/2018/7402795